Endothelial vascular cell adhesion molecule-1 (VCAM-1) and its ligand, α4β1 integrin, are key mediators of leukocyte recruitment. These molecules play a role in the development of multiple sclerosis which is associated with leucocyte recruitment and subsequent inflammation, demyelination and axonal loss in the central nervous system. VCAM-1 and its ligand, α4β1 integrin, are important mediators of mononuclear leucocyte recruitment and lesion initiation. VCAM-1 is not constitutively expressed on cerebral vascular endothelium, but is upregulated with endothelial activation. Selective blockade of this interaction in experimental autoimmune encephalitis results in abolition of both lymphocyte recruitment and the paralysis that usually follows.
There is also a close association of tumour colonies with the existing cerebral vasculature in both murine models of brain metastasis and human brain tissue containing metastases. Activation of the vascular endothelium is likely to occur during metastasis development. There is also evidence to suggest that tumour cells use inducible CAMs to promote their adhesion to the vascular endothelium. VCAM-1 has been found to be upregulated in lung and liver metastasis.
Antibodies to human VCAM-1 may be useful in the diagnosis and treatment of diseases and disorders associated with upregulation of VCAM-1 expression, such as multiple sclerosis and tumour metastasis. Currently available antibodies are not suitable for this purpose, and improved antibodies are required.